Track and Field Practice and Bone Outcomes among Adolescents: A Pilot Study (ABCD-Growth Study).
Osteoporosis is considered a public health problem with high worldwide prevalence. One approach to prevention is through the promotion of physical activity, especially exercise, during adolescence. This study compared bone variables in different body segments in adolescents according to participation in track and field. The study included 34 adolescents (22 boys), of whom 17 were track and field athletes and 17 were control subjects. Bone mineral density (BMD, g/cm2) and bone mineral content (BMC, g) were analyzed using dual energy X-ray absorptiometry (total body stratified by body segments). Peak height velocity was used to estimate somatic maturation. Athletes had higher BMD (P=0.003) and BMC (P=0.011) values in the lower limbs and higher whole body BMD (P=0.025) than the control group. However, when adjusted for confounding factors, the difference was not maintained. The groups had similar lean soft tissue values (P=0.094). Training overload was positively correlated with BMD in the upper limbs (r=0.504; 95% confidence interval, 0.031-0.793). Although track and field athletes had higher BMD and BMC values in the lower limbs, these differences were not significant when adjusted for confounding factors. Track and field participation in adolescence appears to influence BMD and BMC in lower limbs, and fat-free mass seems to mediate this effect. Also, higher training loads were found to be positive for bone health in upper limbs.


Temperature and phosphorus: the main environmental factors affecting the seasonal variation of soil bacterial diversity in Nansi Lake Wetland.
The soil bacteria promote the circulation conversion of lake nutrients and play an important role in maintaining the balance of the lake ecosystem. Few studies have investigated the association of seasonal variation in bacteria and environmental factors in inland freshwater lake wetlands. Nansi Lake is a large shallow freshwater lake in northern China. It is an important hub of the eastern route of the South-to-North Water Diversion Project. In this study, bacterial 16S rRNA genes were used to analyze the variation of soil bacterial community diversity in Nansi Lake Wetland and its influencing factors in different seasons. It is showed that the phylum, family, and genus with the largest relative abundance in the soil of Nansi Lake Wetland are Proteobacteria, Nitrosomonadaceae, and MND1, respectively. There were significant seasonal differences in soil bacterial diversity in Nansi Lake Wetland, which was significantly higher in summer than in winter. Seasonal variation in environmental factors was significantly correlated with the variation in bacterial communities. Temperature and the content of available phosphorus may be the key factors influencing seasonal variation in bacterial diversity. The results of this study further enhance our understanding of the relationship between bacterial community diversity and environmental factors in the lake wetland ecosystem, which can provide scientific data for the conservation of Nansi Lake Wetland.


The benefits of comprehensive care of hemophilia: a five-year study of outcomes.
Eleven of 22 federally funded Comprehensive Hemophilia Centers have collected data on outcomes, before and after five years of this program's existence. Improved health, decreased hospitalization, decreased absenteeism, and a decrease in the unemployment rate from 36 per cent to 13 per cent were accompanied by decreased costs of care. In this model of a chronic handicapping illness, the early application of comprehensive care is preferable to the previous emphasis on end-stage rehabilitative efforts.


Improvements in newborn care and newborn resuscitation following a quality improvement program at scale: results from a before and after study in Tanzania.
Every year, more than a million of the world's newborns die on their first day of life; as many as two-thirds of these deaths could be saved with essential care at birth and the early newborn period. Simple interventions to improve the quality of essential newborn care in health facilities - for example, improving steps to help newborns breathe at birth - have demonstrated up to 47% reduction in newborn mortality in health facilities in Tanzania. We conducted an evaluation of the effects of a large-scale maternal-newborn quality improvement intervention in Tanzania that assessed the quality of provision of essential newborn care and newborn resuscitation. Cross-sectional health facility surveys were conducted pre-intervention (2010) and post intervention (2012) in 52 health facilities in the program implementation area. Essential newborn care provided by health care providers immediately following birth was observed for 489 newborns in 2010 and 560 in 2012; actual management of newborns with trouble breathing were observed in 2010 (n = 18) and 2012 (n = 40). Assessments of health worker knowledge were conducted with case studies (2010, n = 206; 2012, n = 217) and a simulated resuscitation using a newborn mannequin (2010, n = 299; 2012, n = 213). Facility audits assessed facility readiness for essential newborn care. Index scores for quality of observed essential newborn care showed significant overall improvement following the quality-of-care intervention, from 39% to 73% (p <0.0001). Health worker knowledge using a case study significantly improved as well, from 23% to 41% (p <0.0001) but skills in resuscitation using a newborn mannequin were persistently low. Availability of essential newborn care supplies, which was high at baseline in the regional hospitals, improved at the lower-level health facilities. Within two years, the quality improvement program was successful in raising the quality of essential newborn care services in the program facilities. Some gaps in newborn care were persistent, notably practical skills in newborn resuscitation. Continued investment in life-saving improvements to newborn care through the health services is a priority for reduction of newborn mortality in Tanzania.


The role of the restorative dentist in the diagnosis and maintenance phases of implant therapy--Part II: Prosthetic planning.
Prosthetic planning is critical to the success of the diagnostic phase of implant therapy and is used to establish fixture numbers, position and the optimal occlusal scheme, based on the design of the definitive prosthesis. The prosthetic needs of the patient, anticipated functional and parafunctional forces, restoration fabrication and serviceability are all considered. A clear picture of the intended rehabilitation is provided to the surgical team and expedites the consultation between implant team members. Comprehensive diagnostic planning using mounted diagnostic casts and diagnostic wax-ups will provide definite parameters for fixture number, position and alignment, and permit the fabrication of radiographic and surgical templates as the treatment sequence progresses. Patients need to be informed of the time and expense involved in the diagnostic phase of implant therapy prior to the initiation of the planning process. The practitioner conducting the selection and planning phase is entitled and should expect financial remuneration commensurate with the time and effort required to achieve the objectives of this phase of implant therapy. The Planning Process Using mounted diagnostic casts and diagnostic wax-ups: 1. Establish fixture numbers and position; 2. Establish the optimal occlusal scheme; 3. Design the definitive prosthesis; 4. Fabricate a surgical template. Design Principles--Summary 1. The location and number of fixtures dictates the prosthetic design and influences restorative success. 2. A restoration must be designed to distribute forces to the fixtures without overloading the bone, and therefore be able to withstand anticipated functional and parafunctional loading. 3. Design for optimal function and esthetics with a regard for patient comfort and maintenance.


A multi-center cross-sectional study on midwives' self-efficacy and influencing factors.
Healthcare professionals who lack self-efficacy may fail to cope with stressful situations, which increases job burnout and turnout. Self-efficacy of midwives with high workload may affect the quality of service. However, little is known about midwives' self-efficacy and related factors. This study aimed to examine the level and influencing factors of self-efficacy among midwives, and to assess the relationships between their self-efficacy and job burnout. This was a multi-center cross-sectional study involving 700 midwives from 33 hospitals in China. Data were collected by three self-administered questionnaires, including a socio-demographic questionnaire, General Self-Efficacy Scale and Maslach Burnout Inventory. Pearson correlation was utilized to analyze the association of self-efficacy with job burnout. A multiple linear regression model was performed to identify variables associated with midwives' self-efficacy. The score of self-efficacy among Chinese midwives was 24.34 ± 5.28. The incidence of job burnout was 52.9%. The influencing factors of self-efficacy among midwives were low personal accomplishment, emotional exhaustion, length of service, interest in the midwifery field, marital status and whether they came from a one-child family or not. Chinese midwives had a moderate level of self-efficacy which easily led to job burnout. Also, several personal-related and work-related factors would affect the self-efficacy of midwives. Nursing managers are called on to attach importance to self-efficacy of midwives and provide effective interventions to improve their self-efficacy.


[Use of noninvasive high-frequency oscillatory ventilation in very low birth weight infants].
Objective: To evaluate the effectiveness and safety of the use of noninvasive high-frequency oscillation ventilation (nHFOV) in very low birth weight infants. Method: A total of 36 cases received nHFOV between January 2016 and October 2016 in Children's Hospital, Zhejiang University School of Medicine, including 24 males and 12 females, with the gestational age of (27.5±2.5) weeks and birth weight of(980±318)g. The data of the ventilator settings, side effects, and changes of the respiratory function before and after nHFOV were collected and analyzed retrospectively. Nonparametric tests or t tests or χ(2) tests were used. Result: Thirty-two (89%) out of the 36 cases successfully avoided intubation or re-intubation after using of nHFOV. nHFOV was used as the rescue treatment after failure of other noninvasive ventilation in 17 cases, and as the prophylactical treatment preventing re-intubation after extubation in the remaining 19 cases. There were significant decreases in the incidences of apnea and desaturation(SpO(2)<0.85), the level of PaCO(2, )and the FiO(2) 24 h after the initiation of the nHFOV as the rescue therapy((1.2±1.1)vs.(6.3±2.1)episodes , (1.1±1.2) vs.(4.3±1.5) episodes, (43±8) vs.(56±10) mmHg, 0.30±0.07 vs. 0.39±0.11, respectively; 1 mmHg=0.133 kPa, t=7.562, 8.913, 4.179, 3.437 respectively, all P<0.01). No significant changes were found in FiO(2) and PaCO(2) levels 24 h after initiation of nHFOV as the prophylactical therapy after extubation (0.42±0.12 vs.0.40±0.10, (49±8)vs.(48±7)mmHg, t=0.872 and 0.501 respectively, both P>0.05), except for the significant decreases in the mean airway pressure ((7.9±2.6)vs.(9.6±1.6)cmH(2)O, 1 cmH(2)0=0.098 kPa, t=2.198, P=0.041). There were 4 cases suffered from nasal septum injury, while no other nHFOV related complications were noted. Conclusion: nHFOV can be applied in preterm infants as a rescue treatment after the failure of other noninvasive ventilation, or prophylactically used in patients who have high risk of re-intubation.


Determination of gag subtypes of HIV type 1 detected among female sex workers in Calcutta, India.
HIV-1 subtyping is important to study the changing scenario of genetic variation. The gag-based heteroduplex mobility assay (gag-HMA) was developed and evaluated as a powerful and reliable technique for identifying the HIV-1 group M subtypes A to H and the circulating recombinant forms (CRFs). To study the subtype distribution of HIV-1 strains from the eastern part of India, we used the gag-based HMA, followed by the sequencing and phylogenetic analysis. Blood samples from HIV-1-seropositive female sex workers in Calcutta were subjected to gag-HMA. The most prevalent subtype was found to be the C type, among which the C4 subsubtype was prevalent. However, a number of nontypable C strains were found in gag-HMA. Phylogenetic analysis revealed the discrete nature of the C strains and no monophyletic cluster was noticed. This result might indicate a growing tendency of variations among the HIV-1 type C strains circulating in eastern India.


The distribution of halofenate in plasma: a comparative analysis using Scatchard vs. stepwise association constants.
The distribution of Halofenate between the free and albumin bound forms was calculated by the use of two computer programs using both Scatchard association constants for a 3,3,7 model, and six stepwise equilbrium constants over a range of drug concentrations reported in man. The calculations, using either set of constants, showed that only 0.3 to 0.5% of the drug would be free. Using Scatchard association constants, it was estimated that 92 to 95% of the drug would be bound by the high affinity set of sites, and lesser amounts by sites of lesser affinity. A more complex pattern of distribution was obtained with the stepwise equilibrium constants. At low concentrations of Halofenate the complex with one mole of drug/mole of protein was most abundant and at the highest concentration studied the complex with two moles of drug/mole of protein was most abundant.


Decreased phosphatidylcholine biosynthesis and abnormal distribution of CTP:phosphocholine cytidylyltransferase in cholesterol auxotrophic Chinese hamster ovary cells.
Phosphatidylcholine (PtdCho) biosynthesis was examined in the sterol regulatory defective (SRD) Chinese hamster ovary (CHO) cell line SRD 6. SRD 6 cells do not display transcriptional activation of sterol-regulated genes and are cholesterol auxotrophs. Compared to CHO 7 cells (parental line from which the SRD cells were derived), incorporation of [3H]choline during a 2-h pulse into PtdCho and sphingomyelin was reduced 3- and 4.5-fold, respectively, in SRD 6 cells grown with or without cholesterol. SRD 6 cells grown in cholesterol-free medium for 24 h had 8% less phosphatidylcholine (PtdCho) mass compared to CHO 7 cells. Consistent with impaired CTP:phosphocholine cytidylyltransferase activity, [3H]choline-labeled SRD 6 cells had elevated [3H]phosphocholine and delayed conversion to [3H]PtdCho during a 2-h chase period. Compared to CHO 7 cells, cytosolic cytidylyltransferase activity was elevated 2- to 3-fold in SRD 6 cells grown in the absence of cholesterol, but activity in the total membrane fraction was normal. Immunoblot analysis confirmed that cytidylyltransferase mass was increased 2-fold in SRD 6 total cell extracts and cytosol, but not membranes. The amount of [32P]phosphate-labeled cytidylyltransferase in cytosol and membranes of SRD 6 cells were similar to controls. Likewise, cytidylyltransferase mRNA levels were not significantly different between SRD 6 and CHO 7. The defect in PtdCho synthesis in SRD 6 cells could be overcome by treatment with 150 microns oleate, such that after 5 h [3H] choline incorporation into PtdCho and phosphocholine in SRD 6 and CHO 7 cells was similar. Cholesterol auxotrophic SRD 6 cells display reduced PtdCho mass and synthesis and elevated levels of cytosolic cytidylyltransferase, defects that were only partially corrected by growth in exogenous cholesterol. These results indicate a requirement for normal cholesterol regulation and synthesis in the maintenance PtdCho levels and activity of cytidylyltransferase.


8-acetoxy-trisulfopyrene as the first activatable fluorogenic probe for add-and-read assessment of Organic anion-transporting polypeptides, OATP1B1, OATP1B3, and OATP2B1.
Organic anion-transporting polypeptides, OATP1B1, OATP1B3, and OATP2B1 are multispecific membrane proteins mediating the hepatocellular uptake of structurally diverse endo- and exogenous compounds, including various kinds of drugs. Co-administration of OATP1B/2B1 substrates may lead to altered pharmacokinetics or even toxicity. Therefore, the study of the interaction with these OATPs is essential in drug development and is recommended by international regulatory agencies, the FDA, EMA, and PMDA. In general, radiolabeled indicators are used to measure drug interactions of OATPs, and, lately, fluorescent probes are also gaining wider application in OATP tests. However, all of the currently available methods (either radioactive or fluorescence-based) comprise multiple steps, including the removal of the indicator in the end of the experiment. Hence, they are not ideally suited for high-throughput screening. In the current study, in order to find an indicator allowing real-time assessment of hepatic OATP function, we searched for an activatable fluorogenic OATP substrate. Here, we show that 8-acetoxypyrene-1,3,6-trisulfonate (Ace), a fluorogenic derivative of the hepatic OATP substrate pyranine (8-hydroxypyrene-1,3,6-trisulfonate) enters the cells via OATP1B1/3 or OATP2B1 function. In living cells, Ace is then converted into highly fluorescent pyranine, allowing "no-wash" measurement of OATP function and drug interactions. Furthermore, we demonstrate that Ace can be used in an indirect assay termed as competitive counterflow suitable to distinguish between transported substrates and inhibitors of OATP1B1. The fluorescence-based methods described here are unique and open the way toward high-throughput screening of interactions between new molecular entities and OATPs.


Plasmonic Nanofluids: Enhancing Photothermal Gradients toward Liquid Robots.
In situ energy generation in soft, flexible, autonomous devices is challenging due to the need for highly stretchable and fault-resistant components. Nanofluids with pyro-, tribo-, or thermoelectric properties have recently emerged as promising solutions for realizing liquid-based energy harvesters. Yet, large thermal gradients are required for the efficient performance of these systems. In this work, we show that oil-based plasmonic nanofluids uniquely combine high photothermal efficiency with strong heat localization. In particular, we report that oleic acid-based nanofluids containing TiN nanoclusters (0.3 wt %) exhibit 89% photothermal efficiency and can realize thermal gradients as large as 15.5 K/cm under solar irradiation. We experimentally and numerically investigate the photothermal behavior of the nanofluid as a function of solid fraction concentration and irradiation wavelength, clarifying the interplay of thermal and optical properties and demonstrating a dramatic improvement compared with water-based nanofluids. Overall, these results open unprecedented opportunities for the development of liquid-based energy generation systems for soft, stand-alone devices.


The new therapeutic herbal drug HM0601 and its bioactive compound rutin exert potent antiproliferative activities in mast cells.
HM0601 consists of Allium hookeri and Lycium chinense fruit and contains a lot of rutin. Here, we ascertained whether HM0601 and its major compound rutin reduce proliferation of human mast cell line, HMC-1, under thymic stromal lymphopoietin (TSLP) stimulation. Therapeutic rutin or HM0601 treatment considerably reduced proliferation of mast cells without exposing activated HMC-1 cells to any cytotoxicity. Reduced levels of mouse double minute 2 and phosphorylated signal transducers and activators of transcription 6 were accompanied by treatment with rutin or HM0601. In TSLP-stimulated cells, rutin or HM0601 treatment significantly impaired levels of interleukin (IL)-13 and Bcl2 expression. Notably, rutin or HM0601 treatment returned Bax and phosphorylated p53 protein levels and caspase-3 activities impaired by TSLP. In addition, levels of inflammatory cytokine were considerably reduced by treatment with rutin or HM0601 on TSLP-stimulated cells. In conclusion, these results indicate that HM0601 can be used as a new therapeutic herbal drug for prevention and therapeutic intervention of allergic inflammatory diseases.


[Current status of chemotherapy of gastric and colorectal cancer].
The group of gastric and colorectal carcinomas has the highest cancer mortality in Western Germany. The possibilities of treatment with chemotherapy only have palliative character. 5-Fluourouracil is the therapeutic of choice on the metastasized colorectal cancer. However, a prolongation of survival time by treatment of the colorectal tumor could neither be recorded in applying 5-Fluorouracil as a single agent, nor through combination chemotherapy. The treatment of the metastasized gastric carcinoma with combinations consisting of the 5-Fluorouracil and Adriamycin could be of future value. Also effective with this tumour as a palliative measure is the combined treatment with 5-Fluorouracil and irradiation. The advantage of an adjuvant therapy of a chemotherapeutical, radiological or immunological kind could so far not be proved.


Nordic registry-based cohort studies: Possibilities and pitfalls when combining Nordic registry data.
All five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden) have nationwide registries with similar data structure and validity, as well as personal identity numbers enabling linkage between registries. These resources provide opportunities for medical research that is based on large registry-based cohort studies with long and complete follow-up. This review describes practical aspects, opportunities and challenges encountered when setting up all-Nordic registry-based cohort studies. Relevant articles describing registries often used for medical research in the Nordic countries were retrieved. Further, our experiences of conducting this type of study, including planning, acquiring permissions, data retrieval and data cleaning and handling, and the possibilities and challenges we have encountered are described. Combining data from the Nordic countries makes it possible to create large and powerful cohorts. The main challenges include obtaining all permissions within each country, usually in the local language, and retrieving the data. These challenges emphasise the importance of having experienced collaborators within each country. Following the acquisition of data, data management requires the understanding of the differences between the variables to be used in the various countries. A concern is the long time required between initiation and completion. Nationwide Nordic registries can be combined into cohorts with high validity and statistical power, but the considerable expertise, workload and time required to complete such cohorts should not be underestimated.


Characterization of the interaction of a recombinant soluble neuroligin-1 with neurexin-1beta.
Neuroligins, proteins of the alpha/beta-hydrolase fold family, are found as postsynaptic transmembrane proteins whose extracellular domain associates with presynaptic partners, proteins of the neurexin family. To characterize the molecular basis of neuroligin interaction with neurexin-beta, we expressed five soluble and exportable forms of neuroligin-1 from recombinant DNA sources, by truncating the protein before the transmembrane span near its carboxyl terminus. The extracellular domain of functional neuroligin-1 associates as a dimer when analyzed by sedimentation equilibrium. By surface plasmon resonance, we established that soluble neuroligins-1 bind neurexin-1beta, but the homologous alpha/beta-hydrolase fold protein, acetylcholinesterase, failed to associate with the neurexins. Neuroligin-1 has a unique N-linked glycosylation pattern in the neuroligin family, and glycosylation and its processing modify neuroligin activity. Incomplete processing of the protein and enzymatic removal of the oligosaccharides chain or the terminal sialic acids from neuroligin-1 enhance its activity, whereas deglycosylation of neurexin-1beta did not alter its association capacity. In particular, the N-linked glycosylation at position 303 appears to be a major determinant in modifying the association with neurexin-1beta. We show here that glycosylation processing of neuroligin, in addition to mRNA splicing and gene selection, contributes to the specificity of the neurexin-beta/neuroligin-1 association.


16-Aza-ent-beyerane and 16-Aza-ent-trachylobane: potent mechanism-based inhibitors of recombinant ent-kaurene synthase from Arabidopsis thaliana.
The secondary ent-beyeran-16-yl carbocation (7) is a key branch point intermediate in mechanistic schemes to rationalize the cyclic structures of many tetra- and pentacyclic diterpenes, including ent-beyerene, ent-kaurene, ent-trachylobane, and ent-atiserene, presumed precursors to >1000 known diterpenes. To evaluate these mechanistic hypotheses, we synthesized the heterocyclic analogues 16-aza-ent-beyerane (12) and 16-aza-ent-trachylobane (13) by means of Hg(II)- and Pb(IV)-induced cyclizations onto the Delta12 double bonds of tricyclic intermediates bearing carbamoylmethyl and aminomethyl groups at C-8. The 13,16-seco-16-norcarbamate (20a) was obtained from ent-beyeran-16-one oxime (17) by Beckmann fragmentation, hydrolysis, and Curtius rearrangement. The aza analogues inhibited recombinant ent-kaurene synthase from Arabidopsis thaliana (GST-rAtKS) with inhibition constants (IC50 = 1 x 10-7 and 1 x 10-6 M) similar in magnitude to the pseudo-binding constant of the bicyclic ent-copalyl diphosphate substrate (Km = 3 x 10-7 M). Large enhancements of binding affinities (IC50 = 4 x 10-9 and 2 x 10-8 M) were observed in the presence of 1 mM pyrophosphate, which is consistent with a tightly bound ent-beyeranyl+/pyrophosphate- ion pair intermediate in the cyclization-rearrangement catalyzed by this diterpene synthase. The weak inhibition (IC50 = 1 x 10-5 M) exhibited by ent-beyeran-16-exo-yl diphosphate (11) and its failure to undergo bridge rearrangement to kaurene appear to rule out the covalent diphosphate as a free intermediate. 16-Aza-ent-beyerane is proposed as an effective mimic for the ent-beyeran-16-yl carbocation with potential applications as an active site probe for the various ent-diterpene cyclases and as a novel, selective inhibitor of gibberellin biosynthesis in plants.


The preembryo as potential: a reply to John A. Robertson.
... In conclusion, let me agree with Robertson that reasonable persons may indeed disagree on concrete conclusions touching preembryo freezing, discard, research, and diagnosis. But it is one of the challenges to reasonable people to give reasons for their conclusions. When Robertson notes that preembryo research "has been found acceptable by most bodies that have examined the subject," he leaves unstated the fact that many of these bodies have not given reasons for their conclusions. This is especially true of the Warnock Committee. It is definitely not true of John Robertson. He has attempted to give analytic support for his rather permissive positions. I find this support too fragile for its assigned task, though I hasten to say that this does not mean that only a totally prohibitive position is defensible or is mine. Prima facie still means prima facie.


Association Between Medication Use and Bullous Pemphigoid: A Systematic Review and Meta-analysis.
The association between the use of medications and the development of bullous pemphigoid (BP) is unclear. To assess the associations between previous exposure to certain medications and BP. For this systematic review and meta-analysis, PubMed, the Cochrane Central Register of Controlled Trials, and Embase were searched for relevant studies from inception to February 20, 2020. Case-control or cohort studies and randomized clinical trials that examined the odds or risk of BP in patients with previous medication use were included. No geographic or language limitations were imposed. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guideline was followed. The Newcastle-Ottawa Scale was used to evaluate the risk of bias of included observational studies; Cochrane Collaboration's tool was used for randomized clinical trials. Aggregate data were used to conduct a random-effects model meta-analysis if the included studies were sufficiently homogenous. Subgroup analyses were performed for use of various medications of the same category. Odds ratio (OR), hazard ratio, and risk ratio of bullous pemphigoid in association with medication use. This meta-analysis included 13 case-control studies, 1 cohort study, and 1 randomized clinical trial with a total of 285 884 participants. The meta-analysis of case-control studies showed a significant association of BP with previous use of aldosterone antagonists (pooled OR, 1.75; 95% CI, 1.28-2.40), dipeptidyl peptidase 4 inhibitors (pooled OR, 1.92; 95% CI, 1.55-2.38), anticholinergics (pooled OR, 3.12; 95% CI, 1.54-6.33), and dopaminergic medications (pooled OR, 2.03; 95% CI, 1.34-3.05). One cohort study found an increased risk of BP among patients receiving dipeptidyl peptidase 4 inhibitors (hazard ratio, 2.38; 95% CI, 1.16-4.88; P = .02). One trial found a higher occurrence of BP in patients with diabetes receiving linagliptin (0.2% in diabetes group vs 0% in the placebo group). The findings of this systematic review and meta-analysis suggest that aldosterone antagonists, dipeptidyl peptidase 4 inhibitors, anticholinergics, and dopaminergic medications are associated with BP. These medications should be judiciously prescribed, particularly in high-risk patients who are elderly and have disabling neurologic disorders.


[Occurrence of antibodies to chlamydial group antigens in the population of the Czech Republic].
A set of 4,178 human blood sera was tested including 3,093 samples collected from blood donors, 624 randomly collected samples. 124 samples collected from persons possibly exposed to Chlamydia infection, and 337 samples from patients of various hospitals in the districts of Brno, Olomouc and Rumburk. All the sera were examined using the complement fixation microtest and the antigen of Chlamydia psittaci for CFR (Bioveta, Ivanovice na Hané, CzR). Moreover, a subset of samples collected from selected groups (n = 209) was tested by CFR using the genus-specific Ornithose-Antigen (Behring, Germany) (n = 209), another subset of 116 samples by indirect immunofluorescence using the biological Chlamydia trachomatis Spot IF (Bio Merieux) (n = 116), and a subset of 224 samples by ELISA for the demonstration of IgG, IgM and IgA class of antibodies using the kit rELISA Medac. Complement fixing antibodies assayed with the Chlamydia psittaci antigen (Bioveta), reached titres of 1.5, 1:10 and 1:20 in 15.5%, 5.29% and 0.48% of the randomly collected samples, respectively. The corresponding values for the tests carried out with the Ornithose-Antigen were 1:10 in 10.9%, 1:20 in 8.9%, 1:40 in 2.9% and 1:80 in 1.4%. ELISA yielded 52.7%, 26.85% and 17.59% positive results in the globulin classes IgG, IgA and IgM, respectively. Antibody titres from 1:20 and from 1:10, determined with the Bioveta antigen, were found in 2.36% and 9.47% within a representative group of blood donors. The corresponding values for the group of the hospitalized patients were 14.54% and 24.93%, respectively, and for the group of persons possibly exposed to Chlamydia infection 2.42% and 8.87% respectively. The indirect immunofluorescence test yielded positive, negative ad doubtful results in 47.41%, 27.59% and 25.0% persons of the latter group. This group showed also a higher percentage (37.07%) of positive results in ELISA in the class IgA than the randomly selected persons.


Decreased plasma testosterone and total thyroxine in desalivated male rats.
Plasma testosterone and total thyroxine were decreased by 50 and 35%, respectively, in submandibular gland extirpated or parotid duct ligated rats treated 27 days earlier. Sixty-two days after surgery, testosterone and total thyroxine were decreased by 20 and 40%, respectively. These changes occurred in the absence of evidence of nutritional impairment or signs of stress, such as adrenal enlargement or thymic involution.


The effect of early catch-up growth on health and well-being in young adults.
To study the effect of catch-up growth in the 1st year on cognition, health-related quality of life (HRQoL), problem behavior and growth in young adults. We included individuals without severe complications and born small for gestational age (SGA; n = 228 for weight, n = 203 for length) or with a low head circumference (HC, n = 178) or a low weight adjusted for length (n = 64) in the Collaborative Project on Preterm and SGA Infants. Neonatal growth was standardized (standard deviation scores for gestational age, SDSGA) according to GA-specific reference charts. Catch-up growth was defined as SDSGA at 1 year of age adjusted for SDSGA at birth. Cognition was defined by the Multicultural Capacity Test-Intermediate Level, HRQoL by the London Handicap Scale (LHS) and the Health Utility Index Mark 3 categorized into 4 levels (Multi-Attribute Utility, MAU), and problem behavior by the Young Adult Self-Report. We adjusted for potential confounders. Most adults were born preterm (93.7%). A higher catch-up growth in the 1st year was associated with better cognition (B = 2.57, 95% CI 0.08-5.05 for weight), less disabilities according to the LHS (B = 2.06, 95% CI 0.35-3.78 for HC) and the MAU (OR = 0.67, 95% CI 0.48-0.95 for HC) and higher final height (B = 0.33, 95% CI 0.18-0.47 for weight; B = 0.41, 95% 0.28-0.55 for length, and B = 0.18, 95% CI 0.04-0.33 for HC) in young adulthood. There are long-term benefits of catch-up growth.


Can We Create an Arteriovenous Fistula for Hemodialysis through 0.5-1.0 cm Incision without Using Vascular Clamps?
Background A native arteriovenous fistula (AVF) is a gold standard for renal replacement therapy, where regular hemodialysis is the mainstay of survival in the majority of patients suffering from end-stage renal disease. Appropriate vascular clamps are routinely used to occlude an artery and a vein before an arteriotomy or a venotomy is done to prevent blood loss and have a clear field and an ease of anastomosis. The title makes one wonder, is it then possible to create an AVF without using vascular clamps? And through incisions as small as 0.5to 1.0 cm? This is made possible by a very simple new technique, presented here, that helps to occlude vessels to create an AVF through minimal access, and minimize blood loss and postoperative pain. Material and Method Total 622 AVFs were created between 1998 and 2019. With regular forceps or an AVF platform (design given), an AVF was created without using a vascular clamp. Total 321 cases were operated with 0.5 to 1.0 cm and 215 cases within 1.5 cm skin incision approach. Results There were ~85% successful functional fistulas. The blood loss was negligible, and only one in three required pain killer in postoperative period. Conclusion A simple new technique described here makes it possible to create a functional AVF through a small incision, without using vascular clamps.


Enhanced electrical property of Ni-doped CoOx hole transport layer for inverted perovskite solar cells.
Ultrathin Ni doped CoOx films were prepared by direct current co-sputtering at room temperature as inorganic hole transport materials for inverted perovskite solar cells. P-type doping was designed to adjust the valence band position of CoOx to match the that of CH3NH3PbI3, which would effectively eliminate the interface barrier. Moreover, the hole extraction ability would be enhanced and the power conversion efficiency of the devices hence increased from 3.68% to 9.60%. The optimized performance was also accompanied by decent stability as a result of its intrinsic stability.


Sudden death in a young female with an under-recognised coronary anomaly.
Anomalies of coronary number and course represent an opinion-dividing topic in cardiopathology, particularly for their relationship with sudden cardiac death.To the best of our knowledge, we herein report the first fatal case of a young female whose coronary anatomy was characterised by the absence of any septal perforator branch in the proximal segment of the LAD.This case could be useful for pathologists, coronary angiographers, and interventional cardiologists in detecting this infrequent anomaly, thus providing a more accurate estimation of its incidence. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3570015858473043.


Equidistant Response Options on Likert-Type Instruments: Testing the Interval Scaling Assumption Using Mplus.
The purpose of the present study was to provide the means to evaluate the "interval-scaling" assumption that governs the use of parametric statistics and continuous data estimators in self-report instruments that utilize Likert-type scaling. Using simulated and real data, the methodology to test for this important assumption is evaluated using the popular software Mplus 8.8. Evidence on meeting the assumption is provided using the Wald test and the equidistant index. It is suggested that routine evaluations of self-report instruments engage the present methodology so that the most appropriate estimator will be implemented when testing the construct validity of self-report instruments.


Labels, Gender-Role Conflict, Stigma, and Attitudes Toward Seeking Psychological Help in Men.
Despite a comparable need, research has indicated that on average men hold more negative attitudes toward psychological help seeking than women. Several researchers have suggested that the gender gap in service use and attitudes could be addressed through efforts to better market psychological services to men; however, a limited number of studies have tested this hypothesis. This study examined whether altering the labels for mental health providers (psychologist or counselor), settings (mental health clinic or counseling center), and treatments (problem or feeling focused) could result in less perceived stigma (social and self) by men. Participants, 165 male college students, were asked to read one of eight randomly assigned vignettes that described a man who was experiencing symptoms of depression and was considering seeking help. The vignettes differed in the labels that were used to describe the help that was being considered. Participants then completed measures assessing the stigma (self and social) associated with the treatment, and their preexisting experience of gender-role conflict and attitudes toward psychological help seeking. In summary, perceived stigma did not depend on the type of label that was used; however, 59% of the variance in attitudes was predicted by self-stigma (uniquely explaining 11%), gender-role conflict (uniquely explaining 10%), and social stigma (uniquely explaining 5%). Specifically, higher levels of gender-role conflict, social stigma, and self-stigma were associated with more negative attitudes toward psychological help seeking. Based on the demographics of the sample, these findings primarily have implications for Caucasian college-educated young adult men. Further limitations with the study and recommendations for future research are discussed.


Redox Modulation of PTEN Phosphatase Activity by Hydrogen Peroxide and Bisperoxidovanadium Complexes.
PTEN is a dual-specificity protein tyrosine phosphatase. As one of the central tumor suppressors, a thorough regulation of its activity is essential for proper cellular homeostasis. The precise implications of PTEN inhibition by reactive oxygen species (e.g. H2 O2 ) and the subsequent structural consequences remain elusive. To study the effects of PTEN inhibition, bisperoxidovanadium (bpV) complexes serve as important tools with the potential for the treatment of nerve injury or cardiac ischemia. However, their mode of action is unknown, hampering further optimization and preventing therapeutic applications. Based on protein crystallography, mass spectrometry, and NMR spectroscopy, we elucidate the molecular basis of PTEN inhibition by H2O2 and bpV complexes. We show that both molecules inhibit PTEN via oxidative mechanisms resulting in the formation of the same intramolecular disulfide, therefore enabling the reactivation of PTEN under reductive conditions.


Fetal Myocardial Performance Index in the Third Trimester of Pregnancy: Feasibility and Reproducibility of Conventional Spectral Doppler versus Spectral Tissue Doppler Technique.
This study aims to compare completion rates and reproducibility of myocardial performance index (MPI) using conventional spectral Doppler versus tissue Doppler in an unselected high-risk third trimester population. This was a prospective cross-sectional study of high-risk pregnancies at ≥28 + 0 weeks' gestation. Conventional spectral and tissue Doppler MPI of the left ventricle (LV) and right ventricle (RV) was attempted on all patients. Seventy-nine pregnancies were evaluated. LV tissue Doppler MPI was completed more frequently than LV conventional spectral Doppler MPI (63/79, 79.7% vs. 45/79, 55.7%), p-value <0.01. RV tissue Doppler MPI was completed more frequently than RV conventional spectral Doppler MPI (68/79, 86% vs. 42/79, 53.2%), p-value <0.01. In obese subjects (n = 50) LV tissue Doppler MPI was completed more frequently than LV conventional spectral Doppler MPI (37/50, 74% vs. 26/50, 52%), p-value <0.01. RV tissue Doppler MPI was completed more frequently than RV conventional spectral Doppler MPI (40/50, 80% vs. 25/50, 50%), p-value <0.01. intraclass correlation coefficient for all modalities ranged between 0.73 and 0.93, except for LV conventional spectral Doppler intraobserver variability which was 0.22. Tissue Doppler had statistically higher completion rates than conventional spectral Doppler, including the obese subgroup, with evidence of strong reproducibility in the third trimester.


Impact of iron supplementation on patient outcomes for women with abnormal uterine bleeding: a protocol for a systematic review and meta-analysis.
Abnormal uterine bleeding (AUB), which includes heavy menstrual bleeding (HMB), is a common condition placing women at increased risk for developing iron deficiency and iron deficiency anemia (IDA). Depletion of iron stores has negative implications on physical, social, and emotional health, as well as quality of life. Iron supplements are safe, effective, and readily available, while red blood cell (RBC) transfusions have inherent risks including infectious and immune reactions. Despite high prevalence of IDA among women with AUB, there are limited studies on the impact of iron therapies on patient outcomes. This systematic review and meta-analysis will evaluate the impact of iron supplementation on patient outcomes for women with AUB, when compared to combination therapy, no intervention, placebo, or standard of care. We will conduct a systematic review and meta-analysis of randomized controlled trials and observational studies evaluating the impact of iron interventions on patient outcomes for women with AUB. Systematic literature searches will be conducted in major databases including MEDLINE, EMBASE, CENTRAL, CINAHL, and Web of Science. Studies assessing the impact of iron interventions on patient outcomes in women experiencing AUB, in comparison to combination therapy, no intervention, placebo, or standard of care, will be included in the review. Independent reviewers will screen for eligibility, assess risk of bias, and abstract data. Overall certainty of evidence for each outcome will be assessed using the GRADE approach. We will meta-analyze outcomes which are sufficiently homogeneous to summarize intervention effects and narratively synthesize nonhomogeneous outcomes. The main outcomes of interest are hemoglobin levels immediately prior to surgery and post-operatively, number of RBC transfusions, and adverse effects. Secondary outcomes will include length of hospital stay, intraoperative blood loss, adverse and side effects, quality of life, and iron indices. This review will evaluate the impact of iron interventions on patient outcomes in women with IDA secondary to AUB with focus on changes in hematological and iron indices, red blood cell utilization, quality of life, cost of treatment, and adverse events. The results will inform evidence-based clinical practice for the management of iron deficiency and IDA secondary to AUB. PROSPERO CRD42019137282.


The impact of migraine prevention on daily activities: a longitudinal and responder analysis from three topiramate placebo-controlled clinical trials.
Topiramate is approved for the prophylaxis (prevention) of migraine headache in adults. The most common adverse events in the three pivotal, randomized, double-blind, placebo-controlled trials were paresthesia, fatigue, cognitive impairment, anorexia, nausea, and taste alteration. In these trials, topiramate 100 mg/d significantly improved Migraine-Specific Questionnaire (MSQ) scores versus placebo (p < 0.001). The MSQ measures how much migraine limits/interrupts daily performance. Pooled analyses of pivotal trial data were conducted to further assess how topiramate 100 mg/d affects daily activities and patient functioning. Mean MSQ and Medical Outcome Study Short Form 36 (SF-36) change scores (baseline to each double-blind assessment point) were calculated for pooled intent-to-treat (ITT) patients. Additionally, pooled ITT patients receiving topiramate 100 mg/d or placebo were combined and divided into two responder groups according to percent reduction in monthly migraine frequency: < 50% responders or >or= 50% responders. Between-group differences were assessed using analysis of covariance. Of 756 patients (mean age 39.8 years, 86% female), 384 received topiramate 100 mg/d and 372 placebo. Topiramate significantly improved all three MSQ domains throughout the double-blind phase versus placebo (p = 0.024 [week 8], p < 0.001 [weeks 16 and 26] for role prevention; p < 0.001 for role restriction and emotional function [all time points]). Topiramate 100 mg/d significantly improved SF-36 physical component scores (PCS) throughout the double-blind phase versus placebo (p < 0.001, all time points) and significantly improved mental component scores (MCS) at week 26 (p = 0.043). The greatest topiramate-associated improvements on SF-36 subscales were seen for bodily pain and general health perceptions (p < 0.05; weeks 8, 16, and 26), and physical functioning, vitality, role-physical, and social functioning (p < 0.05; weeks 16 and 26). Significantly greater improvements in all three MSQ domains, as well as the PCS and MCS of SF-36, were observed for >or= 50% responders versus < 50% responders (p < 0.001). Significantly greater percentages of topiramate-treated patients were >or= 50% responders versus placebo (46% versus 23%; p < 0.001). Topiramate 100 mg/d significantly improved daily activities and patient functioning at all time points throughout the double-blind phase. Daily function and health status significantly improved for those achieving a >or= 50% migraine frequency reduction.


Massively parallel sequencing and genome-wide copy number analysis revealed a clonal relationship in benign metastasizing leiomyoma.
Benign metastasizing leiomyoma (BML) is a rare disease entity typically presenting as multiple extrauterine leiomyomas associated with a uterine leiomyoma. It has been hypothesized that the extrauterine leiomyomata represent distant metastasis of the uterine leiomyoma. To date, the only molecular evidence supporting this hypothesis was derived from clonality analyses based on X-chromosome inactivation assays. Here, we sought to address this issue by examining paired specimens of synchronous pulmonary and uterine leiomyomata from three patients using targeted massively parallel sequencing and molecular inversion probe array analysis for detecting somatic mutations and copy number aberrations. We detected identical non-hot-spot somatic mutations and similar patterns of copy number aberrations (CNAs) in paired pulmonary and uterine leiomyomata from two patients, indicating the clonal relationship between pulmonary and uterine leiomyomata. In addition to loss of chromosome 22q found in the literature, we identified additional recurrent CNAs including losses of chromosome 3q and 11q. In conclusion, our findings of the clonal relationship between synchronous pulmonary and uterine leiomyomas support the hypothesis that BML represents a condition wherein a uterine leiomyoma disseminates to distant extrauterine locations.


[Pregnancy induced changes in lipid-lipoprotein serum profile in women and newborn birth weight].
The pregnancy is associated with hyperlipoproteinemia including an increased level of total cholesterol, LDL-cholesterol, HDL2 and HDL3-cholesterol and triglycerides. The mechanism of pregnancy associated hyperlipoproteinemia remain unclear. The aim of the study was to estimate the relationship between the newborn body mass at delivery and changed by pregnancy lipid-lipoprotein blood profile in women. Studies were carried out in the cases of 67 women. Blood samples were studied at 25 week of pregnancy, during the labor, and at 5th day after delivery. No influence of the pregnancy-changed lipid-lipoprotein pattern of the mothers on the body mass of newborns was found in any of the investigated period.


[Emphysematous cystitis due to Clostridium perfringens--a localised infection in a man with generalized melanoma].
Emphysematous cystitis was found at autopsy of a 47-year-old man suffering from generalised malignant melanoma. Bacteriological cultures from the urinary bladder showed Escherichia coli, Klebsiella sp. and Clostridium perfringens type A, toxic strain. The histological examination revealed cystic dilatation of lymphatic vessels both in bladder mucosa and muscularis propria. There were multinucleated macrophages in the lining of some of these cystic spaces and a few Gram-positive rods inside their lumina. In the mucosal and submucosal connective tissue there were signs of chronic inflammation and, focally, small haemorrhages. We suppose that the gas production was due to the presence of Clostridium perfringens and believe that the infection of the urinary bladder occurred in relation to the repeated insertion of the catheter into the bladder of a patient with secondary immunosuppression. Emphysematous cystitis was, in our case, a localised clostridial infection without clinical and morphological signs of generalised septicaemia.


THEILERIOSIS IN MOUNTAIN BONGO REPATRIATED TO KENYA: A CLINICAL AND MOLECULAR INVESTIGATION.
Mountain bongo (Tragelaphus euryceros isaaci) from Kenya were exported to zoological institutions in North America and Europe in the 1970s and 1980s. In the following 20-30 years bongo numbers declined in Kenya and the Mountain Bongo Repatriation Project was launched. This resulted in 18 adult bongo, descendants of the original translocated bongo, being repatriated from the United States to Kenya in 2004. These newly arrived bongo were inadvertently exposed to heavy tick infestation on release in a conservancy on the slopes of Mount Kenya. Mortality and morbidity occurred during the third week after arrival. Theileria sp. infection was apparent from the history, clinical signs, and necropsy findings, and Theileria-like parasites were detected microscopically in samples from sick and dead animals. Four bongo died before the outbreak was controlled. In order to identify the Theileria parasite conclusively, molecular amplification techniques were used. A combination of reverse line blotting, with small subunit ribosomal RNA (SSU rRNA) polymerase chain reaction (PCR) amplification and nucleotide sequencing, identified the protozoan parasite Theileria taurotragi, suggesting this as the most probable cause of mortality and morbidity in the repatriated bongo.


Searching for the relationship between the parameters of metabolic syndrome and the rs17782313 (T>C) polymorphism of the MC4R gene in postmenopausal women.
Metabolic syndrome (MS) is widespread in the human population, and its incidence is continuously increasing, generating serious health problems. The purpose of this study was to find the relationship between the parameters of MS and the melanocortin type 4 receptor (MC4R) gene polymorphism in postmenopausal women. The study involved 344 healthy Polish women, who had their last menstrual cycle 1 year ago or earlier. The study included blood analysis, survey, and body measurements. The mean age was 58.5±6.6 years. An increased body mass index was observed in 65.7% and abdominal obesity in 80.3% of the study population. MS was diagnosed in 40.7% of all participants, including 39.3% of women with the T/T genotype and 44.7% of those with the C/X genotype (χ2 test; P>0.05). A logistic regression model showed that the probability of MS was higher in patients with the C/X genotype (odds ratio =1.25) (χ2 test; P>0.05). The study concluded that MS is a very common condition among postmenopausal women. The C/X genotype of the MC4R gene seems to predispose postmenopausal women to developing some MS symptoms.


[Allergic morbidity in children of female workers at a Tyre factory].
Working conditions and morbidity in tyre female workers and allergic morbidity in their children were studied. The incidence of allergic diseases in the children of tyre female workers constantly subject to poor working conditions was ascertained to be higher than in those of workers unengaged in noxious industry. The higher incidence of allergic diseases in the study group children may be regarded as a result of the mediated effect of deleterious maternal industrial factors on a baby's health, mainly by developing atopic diseases. This is due to the early manifestation and more severe course of allergic diseases.


Connection of a Renal Replacement Therapy or Plasmapheresis Device to the ECMO Circuit.
In patients under extracorporeal membrane oxygenation (ECMO) support requiring renal replacement therapy or plasmapheresis, connecting such extracorporeal therapy device to the ECMO circuit provides many advantages compared with central venous catheterization. However, high pressures of the ECMO circuit limit the usefulness of this technique. We propose a new approach to connect extracorporeal therapy lines to the ECMO circuit. Inlet line is connected to the oxygenator, and outlet line is connected either to the femoral artery antegrade perfusion cannula in case of venoarterial ECMO or to the lateral vent of the return cannula in case of venovenous ECMO. We report the successful management of 21 patients using this connection, with much longer hemofilter average lifetime than previously reported.


One-Pot Synthesis of Cyclomatrix-Type Polyphosphazene Microspheres and Their High Thermal Stability.
Highly cross-linked inorganic and organic hybrid cyclomatrix-polyphosphazenes microspheres (C-PPZs) have been successfully synthesized by a one-pot polymerization technique between hexachlorocyclotriphosphazene and p-phenylenediamine in the presence of triethylamine (TEA), and they were used for enhancing the flame retardancy of epoxy resins (EPs). A thermoset EP was prepared by incorporating different percentages (2, 5, and 10%) of C-PPZs into diglycidyl ether of bisphenol A (DGEBA). The results reveal that the size and morphology of the microspheres can be tuned by varying the synthesis temperature. The average size of C-CPPZs gradually increased from 3.1, 4.9, to 7.8 μm as the temperature was increased from 100, 120, to 200 °C, respectively. The thermogravimetric analysis showed that the C-CPPZ microspheres have good thermal stability up to 900 °C with about ∼10 wt % mass loss for C-CPPZs formed at 200 °C compared to ∼30 wt % mass loss for those obtained at 100 and 120 °C. The 10% loss at 900 °C is much lower than the previous research concerning the thermal stability of cyclophosphazene, in which more weight losses were observed at lower temperatures. The resulting C-CPPZ microspheres were characterized by spectroscopic and imaging techniques including Fourier transform infrared spectroscopy, Raman spectroscopy, X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray spectroscopy, elemental mapping, and X-ray photoelectron spectroscopy.


Multilayer adsorption and wetting of acetone on graphite.
Adsorption/desorption isotherms of acetone on highly oriented pyrolytic graphite have been measured by ellipsometry for temperatures above the bulk triple point. The behavior in the monolayer and submonolayer regime is conventional, with 2D gas-liquid and 2D liquid-solid coexistence regions. Further liquid monolayers grow on top of the completed monolayer. The growth is basically layer-by-layer. For temperatures between 190 K and the triple point a prewetting-type transition occurs with a thin-thick jump of the layer thickness on adsorption but a layer-wise removal of the film on desorption. In this temperature regime the first monolayer is solid and its molecules are oriented perpendicular to the substrate whereas the higher layers are orientationally disordered polar liquid.


Gene-carried hepatoma targeting complex induced high gene transfection efficiency with low toxicity and significant antitumor activity.
The success of gene transfection is largely dependent on the development of a vehicle or vector that can efficiently deliver a gene to cells with minimal toxicity. A liver cancer-targeted specific peptide (FQHPSF sequence) was successfully synthesized and linked with chitosan-linked polyethylenimine (CP) to form a new targeted gene delivery vector called CPT (CP/peptide). The structure of CPT was confirmed by (1)H nuclear magnetic resonance spectroscopy and ultraviolet spectrophotometry. The particle size of CPT/ DNA complexes was measured using laser diffraction spectrometry and the cytotoxicity of the copolymer was evaluated by methylthiazol tetrazolium method. The transfection efficiency evaluation of the CP copolymer was performed using luciferase activity assay. Cellular internalization of the CP/DNA complex was observed under confocal laser scanning microscopy. The targeting specificity of the polymer coupled to peptide was measured by competitive inhibition transfection study. The liver targeting specificity of the CPT copolymer in vivo was demonstrated by combining the copolymer with a therapeutic gene, interleukin-12, and assessed by its abilities in suppressing the growth of ascites tumor in mouse model. The results showed that the liver cancer-targeted specific peptide was successfully synthesized and linked with CP to form a new targeted gene delivery vector called CPT. The composition of CPT was confirmed and the vector showed low cytotoxicity and strong targeting specificity to liver tumors in vitro. The in vivo study results showed that interleukin-12 delivered by the new gene vector CPT/DNA significantly enhanced the antitumor effect on ascites tumor-bearing imprinting control region mice as compared with polyethylenimine (25 kDa), CP, and other controls, which further demonstrate the targeting specificity of the new synthesized polymer. The synthesized CPT copolymer was proven to be an effective liver cancer-targeted vector for therapeutic gene delivery, which could be a potential candidate for targeted cancer gene therapy.


Underuse of medication for circulatory disorders among unmarried women and men in Norway?
It is well established that unmarried people have higher mortality from circulatory diseases and higher all-cause mortality than the married, and these marital status differences seem to be increasing. However, much remains to be known about the underlying mechanisms. Our objective was to examine marital status differences in the purchase of medication for circulatory diseases, and risk factors for them, which may indicate underuse of such medication by some marital status groups. Using data from registers covering the entire Norwegian population, we analysed marital status differences in the purchase of medicine for eight circulatory disorders by people aged 50-79 in 2004-2008. These differences were compared with those in circulatory disease mortality during 2004-2007, considered as indicating probable differences in disease burden. The unmarried had 1.4-2.8 times higher mortality from the four types of circulatory diseases considered. However, the never-married in particular purchased less medicine for these diseases, or precursor risk factors of these diseases, primarily because of a low chance of making a first purchase. The picture was more mixed for the divorced and widowed. Both groups purchased less of some of these medicines than the married, but, especially in the case of the widowed, relatively more of other types of medicine. In contrast to the never-married, divorced and widowed people were as least as likely as the married to make a first purchase, but adherence rates thereafter, indicated by continuing purchases, were lower. The most plausible interpretation of the findings is that compared with married people, especially the never-married more often have circulatory disorders that are undiagnosed or for which they for other reasons underuse medication. Inadequate use of these potentially very efficient medicines in such a large population group is a serious public health challenge which needs further investigation. It is possible that marital status differences in use of medicines for circulatory disorders combined with an increasing importance of these medicines have contributed to the widening marital status gap in mortality observed in several countries. This also requires further investigation.


Assessment of Changes in Concentration of Total Antioxidant Status, Acute-Phase Protein, and Prolactin in Patients with Osteoarthritis Subjected to a Complex Spa Treatment with Radon Water: Preliminary Results.
Spa treatment brings many clinical benefits such as improved physical activity, pain relief, and improved quality of life. In the literature, there are only few objective studies evaluating changes in metabolism possibly influencing clinical outcomes. The main purpose of our study was the assessment of the effect of spa treatment on changes in concentration of TAS, CRP, and PRL in patients with osteoarthritis. Patients receiving spa treatment were enrolled. TAS, CRP, and PRL levels were obtained using standard tests before the beginning of treatment as well as on days 5 and 18. The study group consisted of n = 35 patients with peripheral joint and spinal osteoarthritis. The control group consisted of 15 people selected from the resort staff, who also suffered from osteoarthritis and had no contact with radon. An increase in TAS concentration was found in the study group following therapy while the control group was characterized by a significant decrease in TAS. On day 5, an increase in TAS concentration was found in both groups, however, with much worse result in the control group. No changes in CRP concentration were statistically significant. PRL concentration was proven to decrease in a statistically significant way after treatment in the study group. This trial is registered with NCT03274128.


Assessment of ICD-9-based case definitions for influenza-like illness surveillance.
Population-based surveillance of influenza routinely relies on administrative medical encounter databases and ICD-9 codes. However, an assessment of the ICD-9 codes used for the Department of Defense (DoD) influenza-like illness (ILI) case definition has not been conducted since 2007. As coding practices may have changed over time, this analysis was done to determine the sensitivity, specificity, and positive predictive value (PPV) of the current ILI case definition and three alternative case definitions for the 2014-2015 influenza season. Influenza laboratory tests conducted on specimens from DoD beneficiaries during the 2014-2015 season were matched to ambulatory and inpatient medical encounters. The current DoD ILI case definition had high sensitivity (92%) but low specificity (30%) and moderate PPV (63%). A more specific ILI case definition utilizing only codes with greater than 75% influenza positivity for the matched laboratory test had high specificity (96%) and PPV (96%) and moderate sensitivity (62%). The current ILI case definition is sufficient for broad, sensitive population-based surveillance; however, an alternative case definition may be more appropriate when there is a need to maximize specificity.


Ralstonia associated with Vapotherm oxygen delivery device--United States, 2005.
In August 2005, a health-care facility in Pennsylvania reported the occurrence of Ralstonia spp. in six patients aged 21 days to 8 years to the Philadelphia Department of Health and CDC. Preliminary laboratory and epidemiologic investigation identified the Vapotherm 2000i oxygen delivery device (Vapotherm Inc., Stevensville, Maryland) as an associated risk factor for recovery of the organism from blood and respiratory tract samples. Although the source of Ralstonia has not yet been identified, Vapotherm has created new infection-control procedures to reduce the risk for infectious disease transmission among patients using their machines. This report summarizes the initial results of this ongoing investigation and provides recommendations to prevent further spread of Ralstonia species in hospitals.


Cystathionine metabolism in methionine auxotrophic and wild-type strains of Saccharomyces cerevisiae.
The role of cystathionine in methionine biosynthesis in wild-type and auxotrophic strains of Saccharomyces cerevisiae was studied. Homocysteine and cysteinerequiring mutants were selected for detailed study. Exogenously supplied cystathionine, although actively transported by all strains tested, could not satisfy the organic sulfur requirements of the mutants. Cell-free extracts of the wild-type, homocysteine, and cysteine auxotrophs were shown to cleave cystathionine. Pyruvic acid and homocysteine were identified as teh products of this cleavage. A mutant containing an enzyme which could cleave cystathionine to homocysteine in cell-free experiments was unable to use cystathionine as a methionine precursor in the intact organisms. The significance of this finding is discussed.


Distance estimate of the active center of D-beta-hydroxybutyrate dehydrogenase from the membrane surface.
D-beta-Hydroxybutyrate dehydrogenase (EC 22.214.171.124) is a membrane-bound, lipid-requiring enzyme which has a reactive sulfhydryl in the vicinity of the active center. The spin-probe-spin-label technique has been used to estimate the distance of separation of the reactive sulfhydryl of D-beta-hydroxybutyrate dehydrogenase from the bilayer surface. The reactive sulfhydryl of the enzyme was derivatized with the maleimide spin-label reagent 4-maleimido-2,2,6,6-tetramethylpiperidinyl-1-oxy in the presence of the cofactor NAD+. The derivatized enzyme, inserted (inlaid orientation) into phospholipid vesicles, was titrated with spin probes, either Mn2+ or Gd3+, until the spin-label EPR spectrum was reduced in amplitude to its residual (limiting) value. From this limiting amplitude, the dipolar interaction coefficient was obtained, which is related to the reciprocal of the distance to the sixth power. The radial distances of closest approach of the paramagnetic Mn2+ and Gd3+ ions to the spin-label nitroxide on the enzyme were found to be 18 and 16 A, respectively. These calculated distances were in accord with those determined by comparison with a phosphatidylcholine calibration system having 2,2-dimethyloxazolidinyl-1-oxy spin-labels located at selected positions along the sn-2 fatty acyl chain. Since the distal nitroxide moiety of the maleimide spin-label (17 A from the bilayer surface) is 8 A from the sulfhydryl addition site, the two limiting distances of immersion of the reactive sulfhydryl within the bilayer are 9 and 25 A. The shorter distance is considered more compatible with facile access of the coenzyme to the active site of the enzyme.


[Capacities of multidetector spiral computed tomography in the planning and postoperative examination of patients undergoing coronary artery bypass surgery].
Multiple investigations show that multidetector spiral computed tomography (MSCT) bypass grafting becomes an alternative to invasive coronary angiography in detecting coronary graft stenoses and occlusions. The investigation retrospectively estimated the patency of aortocoronary and mammary coronary artery anastomoses by MSCT bypass grafting. Examinations were made in 85 (326 anastomoses) patients who had undergone aortocoronary and mammary coronary artery bypass surgery and had MSCT bypass grafting within 3 years after the surgery. In the first year following the surgery, 18 patients with graft stenotic changes, as evidenced by MSCT, underwent intervention coronary angiography, the sensitivity and specificity of which was 100%. The results of clinical and instrumental examinations were also compared with graft incompetence, as shown on MSCT that revealed that MSCT bypass grafting was the only noninvasive technique to evaluate early coronary graft closure both in the absence of clear signs of myocardial ischemia according to the data of exercise tests and in the presence of recurrent angina pectoris.


Introduction: MHC/KIR and governance of specificity.
The MHC controls specificity, to ensure that appropriate immune responses are mounted to invading pathogens whilst maintaining tolerance to the host. It encodes molecules that act as sentinels, providing a snapshot of the health of the interior and exterior of the cell for immune surveillance. To maintain the ability to respond appropriately to any disease requires a delicate balance of expression and function, and many subtleties of the system have been described at the gene, individual and population level. The main players are the highly polymorphic classical MHC class I and class II molecules, as well as some non-classical loci of both types. Transporter associated with antigen processing (TAP) peptide transporters, proteasome components and Tapasin, encoded within the MHC, are also involved in selection of peptide for presentation. The plethora of mechanisms microorganisms use to subvert immune recognition, through blocking these antigen processing and presentation pathways, attests to the importance of HLA in resistance to infection. There is continued interest in MHC genetics in its own right, as well as in relation to KIR, to transplantation, infection, autoimmunity and reproduction. Also of topical interest, cancer immunotherapy through checkpoint inhibition depends on highly specific recognition of cancer peptide antigen and continued expression of HLA molecules. Here, we briefly introduce some background to the MHC/KIR axis in man. This special issue of immunogenetics expands on these topics, in humans and other model species.


[Association of chromosome 17q copy number variation with overall survival of patients with hepatocellular carcinoma and screening of potential target genes].
OBJECTIVE To assess the association of copy number variations (CNVs) in chromosome 17q with the overall survival(OS) of patients with hepatocellular carcinoma(HCC), and to screen for target genes contained in the OS-related CNVs. METHODS A total of 174 HCC cases were enrolled. For 66 patients, the follow-up data was available. High-resolution Agilent Hu-244A array comparative genomic hybridization (aCGH) and Affymetrix U133 Plus 2.0 expression arrays were used to detect CNVs and gene expression of genes from the 17q region, respectively. The association of CNVs and OS was assessed with Log-rank test, Kaplan-Meier survival analysis, and Cox proportional hazards models. The gene expression in HCCs with 17q gain, HCCs without, and non-tumor liver tissues were compared with a Mann-Whitney U test. RESULTS Univariate association analysis showed that copy number gain in 17q25.1-25.3 was significantly associated with reduced OS (Log-rank test, P = 0.00002), and HCC cases with 17q25.1-25.3 gain had a 4.76-fold (95%CI: 2.31-9.81) increased hazard ratio (HR) for death from HCC, as compared to those without the gain. Multivariate Cox proportional hazards regression model revealed 17q25.1-25.3 gain to be an independent prognostic marker for poor OS (HR = 3.17, 95%CI: 1.39-7.26, P = 0.006). The expression levels of 18 genes in 17q25.1-25.3 including SLC9A3R1, GRB2, and TK1 were significantly increased in HCCs with gain than in those without (all P < 0.01) and non-tumor liver tissues (all P < 0.01). CONCLUSION The association of 17q25.1-25.3 gain with reduced OS has indicated that it is a prognostic marker for poor patient survival in HCC, for which SLC9A3R1, GRB2, and TK1 are candidate genes.


Individual decision-making in the causal pathway to addiction: contributions and limitations of rodent models.
The causal pathway from vulnerability to drug use and addiction involves a complex interaction between genetic, environmental, and behavioral factors. An individual can intervene on this causal pathway by two major types of individual decision. There is the inaugural, momentous decision to use a drug for the first time. This decision is influenced by both prior knowledge on the drug and its expected effects, and also by prior self-knowledge on one's own vulnerability. After an individual has used a drug for the first time, there is the decision to repeat drug use. This decision is influenced by the same factors that were involved in the inaugural decision to initiate drug use, except for one crucial difference. The first drug use has now acted on the individual, changing its brain acutely and also potentially persistently in a way that could bias subsequent decision-making in favor of repeated drug use. The goal of this review article is to assess the contributions and limitations of rodent models (i.e., rats, mice) to understand how prior drug use can influence decision-making in a way that favors future drug use. Overall, research on rodents shows that prior drug use can increase impulsive, risky and/or potentially harmful decision-making. However, this does not apparently translate into more drug use when rodents have the choice between a drug and a competing, nondrug option, except when the expected value of the latter is considerably decreased. The delayed drug reward hypothesis is developed to resolve and explain this apparent discrepancy. This novel hypothesis makes several unique predictions, some of them counterintuitive, and suggests that extrapolation of rodent research to humans should not only take into account differences in drug choice situations but also inherent species-specific differences in individual decision-making.


Ectopic canine tooth: a rare cause for maxillary antral mucocoele.
A 40-year-old female presented with a 10 year history of left sided facial pain and occasional purulent nasal discharge, refractory to antibiotics. Dental examination showed 3 missing teeth in left maxilla one of which had no history of extraction. X-ray paranasal sinus showed a bony opacity in the maxillary sinus but nasal endoscopy was normal. C.T. scan revealed a radio-opaque shadow arising from medial wall of left maxillary sinus with a large maxillary mucocoele. Caldwell-Luc procedure was done and an ectopic canine tooth was seen arising from the medial antral wall. Extraction of the tooth with excision of mucocoele resulted in relieving of the symptoms.


Dysphagia caused by anterior cervical osteophytes: a case report.
This 79-year-old man had a several-year history of dysphagia. On presentation, he spoke with difficulty but was not short of breath, and hemoptysis was present. A 17-mm osteophyte anterior to C3-C4 encroached on the posterior aspect of the oral pharynx and esophagus. The patient underwent C3-C6 anterior ostectomy; recovery was complete within 4 weeks.


Decomposition Analysis of Antenatal Care Utilization Inequities in Kembata Tembaro Zone, Southern Ethiopia.
Health equity has emerged as a global issue in the post-2015 Sustainable Development Goals, and Ethiopia is no exception. Despite positive improvements, inequities in maternal health service utilization among demographic groups continue to be one of Ethiopia's significant challenges in decreasing maternal mortality. This study focuses on antenatal care service discrimination among a local poor group known as the "golden hands" community in Ethiopia's Kembata Tembaro zone. The subgroup community consists of outcast artesian groups known as "golden hands," formerly known as "Fuga," who face discrimination in all aspects of life owing to their living conditions and ethnic background. A community-based comparative cross-sectional study was conducted in Ethiopia's Kembata Tembaro, zone in the Southern Nations, Nationalities, and Peoples' Region (SNNPR), from January to February 2022. The study focused on two groups, "golden hands" and "non-golden hands," consisting of women aged 15-49 years. Using stratified and multistage cluster sampling, 1,210 participants were selected, with 440 from golden hand communities and 770 from non-golden hand communities. Data was collected through translated questionnaires, and data quality was rigorously monitored. The concentration curve and index, as well as logistic-based decomposition analysis, were used to examine inequality. The statistical significance threshold was set at p < 0.05 with a 95% confidence interval. This study comprised 1,210 eligible participants, 440 of whom were golden hand community members. Discrimination accounted for 60.23% of the decreased antenatal care (ANC) service use by the golden hand community. Age, urban residence, and wealth index were the most important independent factors with statistically significant contributions to changes owing to differences in effects (discriminated difference). Since ANC service discrimination is prevalent, the government and nongovernmental organizations should take steps to ensure that marginalized groups in society, such as golden hand women, the poor, the uneducated, and rural people, have equal access to service utilization opportunities.


Structure and performance of infectious disease surveillance and response, United Republic of Tanzania, 1998.
To assess the structure and performance of and support for five infectious disease surveillance systems in the United Republic of Tanzania: Health Management Information System (HMIS); Infectious Disease Week Ending; Tuberculosis/Leprosy; Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome; and Acute Flaccid Paralysis/Poliomyelitis. The systems were assessed by analysing the core activities of surveillance and response and support functions (provision of training, supervision, and resources). Data were collected using questionnaires that involved both interviews and observations at regional, district, and health facility levels in three of the 20 regions in the United Republic of Tanzania. An HMIS was found at 26 of 32 health facilities (81%) surveyed and at all 14 regional and district medical offices. The four other surveillance systems were found at <20% of health facilities and <75% of medical offices. Standardized case definitions were used for only 3 of 21 infectious diseases. Nineteen (73%) health facilities with HMIS had adequate supplies of forms; 9 (35%) reported on time; and 11 (42%) received supervision or feedback. Four (29%) medical offices with HMIS had population denominators to use for data analyses; 12 (86%) were involved in outbreak investigations; and 11 (79%) had conducted community prevention activities. While HMIS could serve as the backbone for IDSR in the United Republic of Tanzania, this will require supervision, standardized case definitions, and improvements in the quality of reporting, analysis, and feedback.


Conservative treatment for patients with intermittent claudication.
The effect of pharmacotherapy or supervised exercise training on patients with intermittent claudication was assessed. One hundred patients with stable intermittent claudication due to arteriosclerosis obliterans were analyzed. We divided the patients into 2 groups: patients treated by pharmacotherapy alone (Group A: 39 claudicants) and patients treated by supervised exercise training and pharmacotherapy (Group B: 61 claudicants). The changes in ankle-brachial pressure index (ABI) and recovery time of ABI after a 40-m walk (RT(40)) and absolute claudication distance (ACD) on a treadmill before and after each treatment were assessed. In Group A, RT(40) decreased from 9.5 +/- 5.8 min at the baseline to 6.4 +/- 3.5 min after 6 months (P=0.0002). In Group B, it decreased from 9.7+/-5.2 min at the baseline to 6.3+/-4.2 min after 3 weeks (P<0.0001). In Group A, ACD increased from 249+/-177 m at the baseline to 317+/-168 m after 6 months (P=0.0003). In Group B, it increased from 143+/-90 m at the baseline to 257+/-161 m after 3 weeks (P<0.0001). Hemodynamics and walking ability were improved by either short-term supervised exercise training or midterm pharmacotherapy. RT(40) may be useful for predicting the effect of conservative treatment on intermittent claudication. Greater increases in ACD after treatment can be achieved in claudicants with a shorter RT(40) before conservative treatment.


Acidity enhances the effectiveness of active chemical defensive secretions of sea hares, Aplysia californica, against spiny lobsters, Panulirus interruptus.
Sea hares such as Aplysia californica, gastropod molluscs lacking a protective shell, can release a purple cloud of chemicals when vigorously attacked by predators. This active chemical defense is composed of two glandular secretions, ink and opaline, both of which contain an array of compounds. This secretion defends sea hares against predators such as California spiny lobsters Panulirus interruptus via multiple mechanisms, one of which is phagomimicry, in which secretions containing feeding chemicals attract and distract predators toward the secretion and away from the sea hare. We show here that ink and opaline are highly acidic, both having a pH of approximately 5. We examined if the acidity of ink and opaline affects their phagomimetic properties. We tested behavioral and electrophysiological responses of chemoreceptor neurons in the olfactory and gustatory organs of P. interruptus, to ink and opaline of A. californica within their natural range of pH values, from approximately 5 to 8. Both behavioral and electrophysiological responses to ink and opaline were enhanced at low pH, and low pH alone accounted for most of this effect. Our data suggest that acidity enhances the phagomimetic chemical defense of sea hares.


Protection of Platinum-Based Micromotors from Thiol Toxicity by Using Manganese Oxide.
Platinum-based micromotors have shown many exciting applications when functionalized using gold-thiol chemistry. However, thiols are known to bind to the Pt surface, which can lead to serious deactivation of the catalyst. In this paper, it is demonstrated that MnO2 can be used to protect Pt-based micromotors prior to the thiol treatment, thus fully avoiding the catalyst poisoning. This approach will greatly facilitate the use of the functionalized Pt micromotors for which the thiol toxicity has been a limiting factor.


Facial and gill musculature of polynemid fishes, with notes on their possible relationships with sciaenids (Percomorphacea: Perciformes).
The Polynemidae is a family of primarily marine fishes with eight genera and 42 extant species. Many aspects of their morphology are largely unknown, with few reports about their osteology and barely any information on their myology. This paper describes and illustrates in detail all facial and branchial muscles of representative species of polynemids. Our analysis demonstrates the existence of several remarkable and previously unknown specializations in the polynemid musculature. The aponeurotic and completely independent origin of the pars promalaris of the adductor mandibulae is apparently unique among percomorphs. The differentiation of this section into lateral and medial subsections; the total separation of the promalaris from the retromalaris; the differentiation of the pars primordialis of the levator arcus palatini into external and internal subsections are also uncommon features of polynemids that are shared by sciaenids, thus supporting the hypothesis of a closer relationship between these families.


[Cytogenetic analysis of transitional cell carcinoma of the bladder, stage B (pT2-3a/pN0)].
Muscle-invading urothelial carcinoma of the bladder, stage B of the Jewett-Marshall Scale (T2-T3a/pN0), treated effectively with radical cystectomy, is known to be a highly curable disease. But certain difficulties arise when it comes to apply the traditional morphological factor to the prognosis of this population, partly due to their relative small numbers and the lack of prospective studies on the subject. Apart from the presence or absence of lymph invasion, it is unclear whether the prognostic factors of poor evolution in tumours are also valid in more invasive lesions. This paper presents the cytogenetic study conducted in 7 patients with Stage B urothelial carcinoma in cystectomy portions. All of them showed favourable evolution except for one case with associated profusion of marker chromosomes and tetraploidy. As it has already been shown in Stage T1 vesical carcinoma, this association almost certainly carries a major predictive value of poor prognosis in the muscle-invading localized disease.


Association of seasonal allergic rhinitis is high in Graves' disease and low in painless thyroiditis.
Hashimoto's thyroiditis is thought to be a T-helper cell type 1 (TH1)-dependent disease, but it is not clear whether Graves' disease is T-helper cell type 2 (TH2)-predominant or not. TH1-predominant diseases are infrequently and TH2-predominant diseases are frequently associated with allergic diseases. We examined the prevalence of seasonal allergic rhinitis to Japanese cedar pollen, a typical TH2-associated disease, in patients with Graves' disease (n = 126), painless thyroiditis (n = 46) and Hashimoto's thyroiditis (n = 88), and compared them to healthy controls (n = 766). Gender and age distribution were not different among patient groups and healthy controls, except for the higher age of patients with Hashimoto's thyroiditis. The prevalence of seasonal allergic rhinitis was significantly high in patients with Graves' disease (42.9%, p < 0.05) and low in patients with painless thyroiditis (13.0%, p < 0.01) but was not different in patients with Hashimoto's thyroiditis (26.1%) compared to that of healthy controls (32.6%). When patients with painless thyroiditis were included in Hashimoto's thyroiditis group, the prevalence of seasonal allergic rhinitis was 21.6% and significantly different from that of healthy controls (p < 0.05). These data indicate that Graves' disease is TH2 predominant and painless thyroiditis is a TH1-predominant disease. Our findings suggest that the shift from TH2 toward TH1 immunogenesis may be important for achieving earlier remission of Graves' disease.


Risk assessment for neurotoxic effects.
Regulation of neurotoxicants is generally based on setting allowable doses (exposures) by dividing a no observed adverse effect level (NOAEL) by uncertainty factors that hopefully account for interspecies and intraspecies differences for extrapolations of experimental results obtained in animals to humans. This procedure makes no use of estimates of risk as a function of dose or does it acknowledge any risk at the NOAEL. The purpose of this paper is to illustrate how bioassay data can be used to estimate the risk of neurotoxic effects as a function of dose. In the absence of direct measurements of neurotoxic effects, biomarkers associated with neurotoxic effects can be used as measures of toxicity. In the absence of a definition of an adverse effect, an abnormal level for a measure of toxicity can be established which occurs only in a small fraction of a population which is not exposed to the substance under investigation. Risk is defined as the proportion of a population whose levels of a measure of toxicity equal or exceeds the abnormal level of the measure under study. The procedure is illustrated using data for neurochemical, neurohistological, and behavioral effects of methylenedioxymethamphetamine (MDMA) administered to rats or monkeys. This procedure is more versatile than the NOAEL/uncertainty factor approach since it provides estimates of risk as a function of dose of a potential neurotoxic substance.


Broadening the Scope for Fluoride-Free Synthesis of Siliceous Zeolites.
Siliceous zeolites are ideally suited for emerging applications in gas separations, sensors, and the next generation of low-k dielectric materials, but the use of fluoride in the synthesis significantly hinders their commercialization. Herein, we show that the dry gel conversion (DGC) technique can overcome this problem. Fluoride-free synthesis of two siliceous zeolites-AMH-4 (CHA-type) and AMH-5 (STT-type), has been achieved for the first time using the method. Siliceous *BEA-, MFI-, and *MRE-type zeolites have also been synthesized to obtain insights into the crystallization process. Charge-balancing interactions between the inorganic cation, organic structure-directing agent (OSDA), and Si-O- defects are found to be an essential aspect. We quantify this factor in terms of the "OSDA charge/silica ratio" of the as-made zeolites and demonstrate that the DGC technique is broadly applicable and opens up new avenues for fluoride-free siliceous zeolite synthesis.


Identification of the catalytic residues of sequence-specific and histidine-free ribonuclease colicin E5.
Colicin E5 cleaves tRNAs for Tyr, His, Asn and Asp in their anticodons to abolish protein synthesis in Escherichia coli. We previously showed how its C-terminal RNase domain, E5-CRD, recognizes the anticodon bases but the catalytic mechanism remained to be elucidated. Although the reaction products with 5'-OH and 2',3'-cyclic phosphate ends suggested a similar mechanism to those of RNases A and T1, E5-CRD does not have the His residues necessary as a catalyst in usual RNases. To identify residues important for the catalytic reaction, mutants as to all residues within 5 Å from the central phosphorus of the scissile phosphodiester bond were prepared. Evaluation of the killing activities of the mutant colicins and the RNase activities of the mutant E5-CRDs suggested direct involvement of Arg33, Lys25, Gln29 and Lys60 in the reaction. Particularly, Arg33 plays a critical role and Ile94 provides a structural support of Arg33. Crystal structure of the complex of E5-CRD(R33Q)/dGpdUp showed structural and binding functional integrity of this mutant protein, suggesting involvement of Arg33 in the catalytic reaction. The structure of the free E5-CRD, we also determined, showed great flexibility of a flap region, which facilitates the access of Lys60 to the substrate in an induced-fit manner.


Up-Regulated Expression of ICAM1, MT1A, PTGS2, LCE3D, PPARD, and GM-CSF2 Following Solar Skincare Protection and Repair Strategies in a 3-Dimensional Reconstructed Human Skin Model.
Clinical, optical and histological research confirms that solar skin damage continues to pose a threat to human skin health globally despite widespread sunscreen usage and sun awareness campaigns. Despite this, very few studies examine the critical changes in gene expression and DNA repair activity following recommended topical solar protection and repair strategies to ameliorate the harmful effects of ultraviolet, visible light and near-infrared radiation. To investigate alterations in gene expression following topical solar protection and solar repair strategies. Using epidermal keratinocytes and dermal fibroblasts derived from a 3-dimensional reconstructed human skin model, gene expression was assessed via the Genemarkers Standard Skin Panel using 112 genes deploying two analytical techniques: DNA microarray and quantitative real-time PCR exploration. Tissues were inoculated with products then collected after 24 hours following application of solar protection formulations and 16 hours following solar repair formulations (The Essential Six, RATIONALE, Victoria, Australia). A DNA microarray revealed 67 genes that were significantly up-regulated or down-regulated following the treatment. The quantitative real-time PCR revealed that, in comparison to the control, the genes encoding Intercellular Adhesion Molecule 1 (ICAM1), Metallothionein 1A (MT1A), Prostaglandin-Endoperoxide Synthase 1 (PTGS2), Late Cornified Envelope 3D (LCE3D), Peroxisome Proliferator Activated Receptor (PPARD), and Granulocyte/Macrophage Colony Stimulating Factor 2 (GM-CSF2) have been up-regulated following usage of the solar protection regime, 1.87, 861.16, 4.34, 1.91, 1.06, and 3.6, respectively. ICAM1, MT1A, PTGS2, LCE3D, PPARD, and GM-CSF2 were up-regulated following use of the solar repair regime, 3.78, 2.98, 14.89, 5.09, 2.42, and 13.51, respectively. This study demonstrates that a specific solar protection and repair regime upregulated genes involved in photoprotection and repair mechanisms in a 3-dimensional (3D) reconstructed human-like skin model.


LISTA, LISTA-HOP and LISTA-HON: a comprehensive compilation of protein encoding sequences and its associated homology databases from the yeast Saccharomyces.
We continued our effort to make a comprehensive database (LISTA) for the yeast Saccharomyces cerevisiae. In this database each sequence has been attributed a single genetic name. In the case of duplicated sequences a simple method has been applied to distinguish between sequences of one and the same gene from non-allelic sequences of duplicated genes. If necessary, synonyms are given in the case of allelic duplicated sequences. Thus sequences can be found either by the name or by synonyms given in LISTA. Each entry contains the genetic name, the mnemonic from the EMBL data bank, the codon bias, reference of the publication of the sequence, Chromosomal location as far as known, Swissprot and EMBL accession numbers. To obtain more information on the included sequences, each entry has been screened against non-redundant nucleotide and protein data bank collections resulting in LISTA-HON and LISTA-HOP. The LISTA data base can be linked to the associated data sets or to nucleotide and protein banks by the Sequence Retrieval System (SRS).


Design, modeling, expression, and chemoselective PEGylation of a new nanosize cysteine analog of erythropoietin.
Recombinant human erythropoietin (rhEPO) is considered to be one of the most pivotal pharmaceutical drugs in the market because of its clinical application in the treatment of anemia-associated disorders worldwide. However, like other therapeutic proteins, it does not have suitable pharmacokinetic properties for it to be administrated at least two to three times per week. Chemoselective cysteine PEGylation, employing molecular dynamics and graphics in in silico studies, can be considered to overcome such a problem. A special kind of EPO analog was elicited based on a literature review, homology modeling, molecular dynamic simulation, and factors affecting the PEGylation reaction. Then, cDNA of the selected analog was generated by site-directed mutagenesis and subsequently cloned into the expression vector. The construct was transfected to Chinese hamster ovary/dhfr(-) cells, and highly expressed clones were selected via methotrexate amplification. Ion-immobilized affinity and size exclusion (SE) chromatography techniques were used to purify the expressed analog. Thereafter, chemoselective PEGylation was performed and a nanosize PEGylated EPO was obtained through dialysis. The in vitro biologic assay and in vivo pharmacokinetic parameters were studied. Finally, E31C analog Fourier transform infrared, analytical SE-high-performance liquid chromatography, zeta potential, and size before and after PEGylation were characterized. The findings indicate that a novel nanosize EPO31-PEG has a five-fold longer terminal half-life in rats with similar biologic activity compared with unmodified rhEPO in proliferation cell assay. The results also show that EPO31-PEG size and charge versus unmodified protein was increased in a nanospectrum, and this may be one criterion of EPO biologic potency enhancement. This kind of novel engineered nanosize PEGylated EPO has remarkable advantages over rhEPO.


Clinically unsuspected bilateral malignant pheochromocytoma.
Pheochromocytoma is an uncommon tumor and occurrence of bilateral malignant tumor is extremely rare. Labile hypertension is the common presenting feature of pheochromocytomas. Herein we describe one such case ofbilateral malignant pheochromocytoma, which was clinically silent except for pain and mass in hypochondrium. Histopathology showed features of malignancy along with hyaline globules, which are less described with malignant tumors. Electron microscopy showed neurosecretory granules in tumor cells.